Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

Abstract

Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a risk factor from both public health and agricultural perspectives. In the present in vivo study, a feeding trial was conducted to evaluate the in vivo effect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-a, IL-8, IL-6, IL-1b and interferon-g) and antiinflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/ tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPARg and NF-kB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38a)/mitogen-activated protein kinase 8 ( JNK1)/ mitogen-activated protein kinase 9 ( JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant decrease in the levels of pro-and anti-inflammatory cytokines at both gene expression and protein levels, correlated with a decrease in the levels of other inflammatory mediators, MMP and TIMP. The results also showed that dietary ZEA induces a dramatic reduction in the expressions of NF-kB1 and TAK1/p38a MAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression of PPARg mRNA. The present results suggest that the toxic action of ZEA begins in the upstream of the MAPK signalling pathway by the inhibition of TAK1, a MAPK/NF-kB activator. In conclusion, the present study shows that ZEA alters several important parameters of the hepatic cellular immune response. From an economic point of view, these data suggest that, in pigs, ZEA is not only a powerful oestrogenic mycotoxin but also a potential hepatotoxin when administered through the oral route. Therefore, the present results represent additional data from cellular and molecular levels that could be taken into account in the determination of the regulation limit of the tolerance to ZEA.

In vivo toxicity studies of fusarium mycotoxins in the last decade: A review

“…ZEA competitively binds to estrogen receptors and causes alterations in the reproductive tract of laboratory mice, rats, guinea pigs, hamsters and rabbits and domestic animals and it is able to induce liver lesions with subsequent development of hepatocarcinoma and alterations of some enzymatic parameters of the hepatic function in rats, rabbits and gilts. ZEA has been shown to be immunotoxic and hepatotoxic and nephrotoxic and an enhancer of lipid peroxidation (Pistol et al, 2014).…”

“…The results of the diverse interactions of ZEA are manifested by functional and morphological alterations of the reproductive organs (Duca et al, 2012). ZEA is considered to be a risk factor from both public health and agricultural perspectives (Pistol et al, 2014). ZEA levels are regulated in international trade, depending on the end product into which the grain being tested will be incorporated (Summerell and Leslie, 2011).…”

“…In the pig, DON is rapidly and efficiently absorbed, most probably in the upper part of the small intestine, and is mainly excreted in the urine, with no accumulation in tissues (Waché et al, 2009). Moreover, pigs are generally considered to be the most sensitive animal species to ZEA and its metabolites (Pistol et al, 2014). In the case of FB1 male pigs have higher immune sensitivity as compared to female pigs (Lallès et al, 2010).…”

“…Zearalenone. ZEA caused severe hepatic immunosuppression (significant reduction in the expression and protein concentrations of several markers of pro-and anti-inflammatory processes) by inhibiting the gene expression and protein concentrations which might have important consequences during an infection process (Pistol et al, 2014).…”

Use of modified halloysite nanotubes in the feed reduces the toxic effects of zearalenone on sow reproduction and piglet development

“…They are frequently found in foods predominantly cereals and forages [2,3]. Both the risk of substantial economic losses and the threat to human health could result from exposure to the toxins [4].…”